ANTIBODY-TARGETED PHOTOLYSIS - INVITRO STUDIES WITH SN(IV) CHLORIN E6 COVALENTLY BOUND TO MONOCLONAL-ANTIBODIES USING A MODIFIED DEXTRAN CARRIER

被引:40
作者
RAKESTRAW, SL
TOMPKINS, RG
YARMUSH, ML
机构
[1] RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,POB 909,PISCATAWAY,NJ 08855
[2] MIT,DEPT CHEM ENGN,CTR BIOTECHNOL PROC ENGN,CAMBRIDGE,MA 02139
[3] RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08855
[4] HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,BOSTON,MA 02114
关键词
antibody modification; immunoconjugates; photosensitization; tumor cells;
D O I
10.1073/pnas.87.11.4217
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugate was prepared by a technique involving the site-specific covalent modification of the monoclonal antibody oligosaccharide moiety. Dextran carriers were synthesized with a single chain-terminal hydrazide group, which was used as the coupling point between the carrier and the monoclonal antibody carbohydrate. Selective in vitro photolysis of SK-MEL-2 human malignant melanoma cells was accomplished using several conjugates prepared from anti-melanoma 2.1 (chromophore:antibody molar ratios, 6.8 and 11.2). Phototoxicity, as measured by clonigenic assay, was dependent on the delivered dose of 634-nm light and was observed only for conjugates that bound SK-MEL-2 cells. As judged by competitive inhibition radioimmunoassay, conjugates prepared in this fashion showed excellent retention of antigen binding activity relative to the unmodified antibody.
引用
收藏
页码:4217 / 4221
页数:5
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